Building block forming a c-c bond upon reaction

ABSTRACT

A building block having the dual capabilities of recognising an encoding element and transferring a functional entity to a recipient reactive group is disclosed. The building block may be used in the generation of a single complex or libraries of different complexes, wherein the complex comprises an encoded molecule linked to an encoding element. Libraries of complexes are useful in the quest for pharmaceutically active compounds.

TECHNICAL FIELD OF THE INVENTION

The present invention relates to a building block comprising acomplementing element and a precursor for a functional entity. Thebuilding block is designed to transfer the functional entity to arecipient reactive group upon recognition between the complementingelement and an encoding element associated with the reactive group.

BACKGROUND

The transfer of a chemical entity from one mono-, di- or oligonucleotideto another has been considered in the prior art. Thus, N. M. Chung etal. (Biochim. Biophys. Acta, 1971, 228, 536-543) used a poly(U) templateto catalyse the transfer of an acetyl group from 3′-O-acetyladenosine tothe 5′-OH of adenosine. The reverse transfer, i.e. the transfer of theacetyl group from a 5′-O-acetyladenosine to a 3′-OH group of anotheradenosine, was also demonstrated.

Walder et al. Proc. Natl. Acad. Sci. USA, 1979, 76, 51-55 suggest asynthetic procedure for peptide synthesis. The synthesis involves thetransfer of nascent immobilized polypeptide attached to anoligonucleotide strand to a precursor amino acid attached to anoligonucleotide. The transfer comprises the chemical attack of the aminogroup of the amino acid precursor on the substitution labile peptidylester, which in turn results in an acyl transfer. It is suggested toattach the amino acid precursor to the 5′ end of an oligonucleotide witha thiol ester linkage.

The transfer of a peptide from one oligonucleotide to another using atemplate is disclosed in Bruick RK et al. Chemistry & Biology, 1996,3:49-56. The carboxy terminal of the peptide is initially converted to athioester group and subsequently transformed to an activated thioesterupon incubation with Ellman's reagent. The activated thioester isreacted with a first oligo, which is 5′-thiol-terminated, resulting inthe formation of a thio-ester linked intermediate. The firstoligonucleotide and a second oligonucleotide having a 3′ amino group isaligned on a template such that the thioester group and the amino groupare positioned in close proximity and a transfer is effected resultingin a coupling of the peptide to the second oligonucleotide through anamide bond.

SUMMARY OF THE INVENTION

The present invention relates to a building block of the generalformula:Complementing Element-Linker-Carrier-Functional entity precursorcapable of transferring a functional entity to a recipient reactivegroup, wherein

-   -   Complementing Element is a group identifying the functional        entity,    -   Linker is a chemical moiety comprising a spacer and a        S—C-connecting group, wherein the spacer is a valence bond or a        group distancing the functional entity precursor to be        transferred from the complementing element and the        S—C-connecting group connects the spacer with the Carrier,    -   Carrier comprises an aromatic-, a saturated- or a partially        saturated heterocyclic ring system, said ring system being mono,        di- or tricyclic and substituted with 0-3 R¹ and containing a        ring-member M belonging to the group consisting of B, Si, Sn and        Zn, whereas M carries the functional entity precursor and 0-2        ligands L selected independently from the group consisting of        —F, -aryl, -heteroaryl, or    -   Carrier is —Ar-M(L)_(p)—, —Ar-(C₁-C₆ alkylene)-M(L)_(p)— or        —Ar—X—(C₁-C₆ alkylene)M(L)_(p)— where Ar is aryl or heteroaryl        substituted with 0-3 R¹, M is B, Sn or Si, X is O, S, or R² and        L is independently chosen from —F, -aryl, -heteroaryl or C₁-C₆        alkyl; R¹ and R¹, are independently selected from —H, —OR², —NR²        ₂, -Halogen, —NO₂, —CN, —C(Halogen)₃, —C(O)R², —C(O)NHR²,        C(O)NR² ₂, —NC(O)R², —S(O)₂NHR², —S(O)₂NR² ₂, —S(O)₂R²,        —P(O)₂—R², —P(O)—R², —S(O)—R², P(O)—OR², —S(O)—OR², —N⁺R² ₃,        wherein p is an integer of 0 to 3 and R² is H, C₁-C₆ alkyl,        C₂-C₆ alkenyl, C₂-C₈ alkynyl, or aryl,    -   Functional entity precursor is H or selected among the group        consisting of a C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₄-C₈        alkadienyl, C₃-C₇ cycloalkyl, C₃-C₇ cycloheteroalkyl, aryl, and        heteroaryl, said group being substituted with 0-3 R³, 0-3 R⁴ and        0-3 R⁷ or C₁-C₃ alkylene-NR³ ₂, C₁-C₃ alkylene-NR³C(O)R⁶, C₁-C₃        alkylene-NR³C(O)OR⁶, C₁-C₂ alkylene-O—NR³ ₂, C₁-C₂        alkylene-O—NR³C(O)R⁶, C₁-C₂ alkylene-O—NR³C(O)OR⁶ substituted        with 0-3 R⁷.    -   where R³ is H or selected independently among the group        consisting of C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₈ alkynyl, C₃-C₇        cycloalkyl, C₃-C₇ cycloheteroalkyl, aryl, heteroaryl, said group        being substituted with 0-3 R⁴ and 0-3 R⁷ and    -   R⁴ is selected independently from —N₃, —CNO, —C(NOH)NH₂, —NHOH,        —NHNH, —C(O), —P(O)(O)₂ or the group consisting of C₂-C₆        alkenyl, C₂-C₆ alkynyl, C₄-C₈ alkadienyl said group being        substituted with 0-2 R⁵,    -   where R⁵ is independently selected from —NO₂, —C(O)O, —C(O),        —CN, —Si₃, —O and —N₂.    -   R⁶ is H, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₇        cycloalkyl, aryl or C₁-C₆ alkylene-aryl substituted with 0-3        substituents independently selected from —F, —Cl, —NO₂, —R²,        —OR², —SiR² ₃        R⁷ is ═O, —F, —Cl, —Br, —I, —CN, —NO₂, —O, —N₂, —N—C(O)R⁶,        —N—C(O)OR⁶, —S, —S(O), —S(O)₂, —COO, —C(O)N₂, or —S(O)₂N₂,

In the following description of the invention the direction ofconnections between the various components of a building block should beread left to right. For example an S—C-connecting group C(═O)—NH— isconnected to a Spacer through the carbon atom on the left and to aCarrier through the nitrogen atom on the right hand side.

The term “C₃-C₇ cycloheteroalkyl” as used herein refers to a radical oftotally saturated heterocycle like a cyclic hydrocarbon containing oneor more heteroatoms selected from nitrogen, oxygen, phosphor, boron andsulphur independently in the cycle such as pyrrolidine (1-pyrrolidine;2-pyrrolidine; 3-pyrrolidine; 4-pyrrolidine; 5-pyrrolidine);pyrazolidine (1-pyrazolidine; 2-pyrazolidine; 3-pyrazolidine;4-pyrazolidine; 5-pyrazolidine); imidazolidine (1-imidazolidine;2-imidazolidine; 3-imidazolidine; 4-imidazolidine; 5-imidazolidine);thiazolidine (2-thiazolidine; 3-thiazolidine; 4-thiazolidine;5-thiazolidine); piperidine (1-piperidine; 2-piperidine; 3-piperidine;4-piperidine; 5-piperidine; 6-piperidine); piperazine (1-piperazine;2-piperazine; 3-piperazine; 4-piperazine; 5-piperazine; 6-piperazine);morpholine (2-morpholine; 3-morpholine; 4-morpholine; 5-morpholine;6-morpholine); thiomorpholine (2-thiomorpholine; 3-thiomorpholine;4-thiomorpholine; 5-thiomorpholine; 6-thiomorpholine); 1,2-oxathiolane(3-(1,2-oxathiolane); 4-(1,2-oxathiolane); 5-(1,2-oxathiolane);1,3-dioxolane (2-(1,3-dioxolane); 4-(1,3-dioxolane); 5-(1,3-dioxolane);tetrahydropyrane; (2-tetrahydropyrane; 3-tetrahydropyrane;4-tetrahydropyrane; 5-tetrahydropyrane; 6-tetrahydropyrane);hexahydropyridazine (1-(hexahydropyridazine); 2-(hexahydropyridazine);3-(hexahydropyridazine); 4-(hexahydropyridazine);5-(hexahydropyridazine); 6-(hexahydropyridazine)), [1,3,2]dioxaborolane,[1,3,6,2]dioxazaborocane.

The term “aryl” as used herein includes carbocyclic aromatic ringsystems of 5-7 carbon atoms. Aryl is also intended to include thepartially hydrogenated derivatives of the carbocyclic systems as well asup to four fused aromatic- or partially hydrogenated rings, each ringcomprising 5-7 carbon atoms.

The term “heteroaryl” as used herein includes heterocyclic unsaturatedring systems containing, in addition to 2-18 carbon atoms, one or moreheteroatoms selected from nitrogen, oxygen and sulphur such as furyl,thienyl, pyrrolyl, heteroaryl is also intended to include the partiallyhydrogenated derivatives of the heterocyclic systems enumerated below.

The terms “aryl” and “heteroaryl” as used herein refers to an aryl whichcan be optionally substituted or a heteroaryl which can be optionallysubstituted and includes phenyl, biphenyl, indenyl, naphthyl(1-naphthyl, 2-naphthyl), N-hydroxytetrazolyl, N-hydroxytriazolyl,N-hydroxyimidazolyl, anthracenyl (1-anthracenyl, 2-anthracenyl,3-anthracenyl), thiophenyl (2-thienyl, 3-thienyl), furyl (2-furyl,3-furyl), indolyl, oxadiazolyl, isoxazolyl, quinazolinyl, fluorenyl,xanthenyl, isoindanyl, benzhydryl, acridinyl, thiazolyl, pyrrolyl(2-pyrrolyl), pyrazolyl (3-pyrazolyl), imidazolyl (1-imidazolyl,2-imidazolyl, 4-imidazolyl, 5-imidazolyl), triazolyl(1,2,3-triazol-1-yl, 1,2,3-triazol-2-yl 1,2,3-triazol-4-yl,1,2,4-triazol-3-yl), oxazolyl (2-oxazolyl, 4-oxazolyl, 5-oxazolyl),thiazolyl (2-thiazolyl, 4-thiazolyl, 5-thiazolyl), pyridyl (2-pyridyl,3-pyridyl, 4-pyridyl), pyrimidinyl (2-pyrimidinyl, 4-pyrimidinyl,5-pyrimidinyl, 6-pyrimidinyl), pyrazinyl, pyridazinyl (3-pyridazinyl,4-pyridazinyl, 5-pyridazinyl), quinolyl (2-quinolyl, 3-quinolyl,4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl, 8-quinolyl), isoquinolyl(1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl,6-isoquinolyl, 7-isoquinolyl, 8-isoquinolyl), benzo[b]furanyl(2-benzo[b]furanyl, 3-benzo[b]furanyl, 4-benzo[b]furanyl,5-benzo[b]furanyl, 6-benzo[b]furanyl, 7-benzo[b]furanyl),2,3-dihydro-benzo[b]furanyl (2-(2,3-dihydro-benzo[b]furanyl),3-(2,3-dihydro-benzo[b]furanyl), 4-(2,3-dihydrobenzo[b]furanyl),5-(2,3-dihydro-benzo[b]furanyl), 6-(2,3-dihydro-benzo[b]furanyl),7-(2,3-dihydro-benzo[b]furanyl), benzo[b]thiophenyl(2-benzo[b]thiophenyl, 3-benzo[b]thiophenyl, 4-benzo[b]thiophenyl,5-benzo[b]thiophenyl, 6-benzo[b]thiophenyl, 7-benzo[b]thiophenyl),2,3-dihydro-benzo[b]thiophenyl (2-(2,3-dihydro-benzo[b]thiophenyl),3-(2,3-dihydro-benzo[b]thiophenyl), 4-(2,3-dihydrobenzo[b]thiophenyl),5-(2,3-dihydro-benzo[b]thiophenyl), 6-(2,3-dihydrobenzo[b]thiophenyl),7-(2,3-dihydro-benzo[b]thiophenyl), indolyl (1-indolyl, 2-indolyl,3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl, 7-indolyl), indazole(1-indazolyl, 3-indazolyl, 4-indazolyl, 5-indazolyl, 6-indazolyl,7-indazolyl), benzimidazolyl (1-benzimidazolyl, 2-benzimidazolyl,4-benzimidazolyl, 5-benzimidazolyl, 6-benzimidazolyl, 7-benzimidazolyl,8-benzimidazolyl), benzoxazolyl (1-benzoxazolyl, 2-benzoxazolyl),benzothiazolyl (1-benzothiazolyl, 2-benzothiazolyl, 4-benzothiazolyl,5-benzothiazolyl, 6-benzothiazolyl, 7-benzothiazolyl), carbazolyl(1-carbazolyl, 2-carbazolyl, 3-carbazolyl, 4-carbazolyl),5H-dibenz[b,f]azepine (5H-dibenz[b,f]azepin-1-yl,5H-dibenz[b,f]azepine-2-yl, 5H-dibenz[b,f]azepine-3-yl,5H-dibenz[b,f]azepine-4-yl, 5H-dibenz[b,f]azepine-5-yl),10,11-dihydro-5H-dibenz[b,f]azepine(10,11-dihydro-5H-dibenz[b,f]azepine-1-yl,10,11-dihydro-5H-dibenz[b,f]azepine-2-yl,10,11-dihydro-5H-dibenz[b,f]azepine-3-yl,10,11-dihydro-5H-dibenz[b,f]azepine-4-yl,10,11-dihydro-5H-dibenz[b,f]azepine-5-yl).

The Functional Entity carries elements used to interact with hostmolecules and optionally reactive elements allowing further elaborationof an encoded molecule of a library. Interaction with host moleculeslike enzymes, receptors and polymers is typically mediated through vander waal's interactions, polar- and ionic interactions and pi-stackingeffects. Substituents mediating said effects may be masked by methodsknown to an individual skilled in the art (Greene, T. W.; Wuts, P. G. M.Protective Groups in Organic Synthesis; 3rd ed.; John Wiley & Sons: NewYork, 1999.) to avoid undesired interactions or reactions during thepreparation of the individual building blocks and during librarysynthesis. Analogously, reactive elements may be masked by suitablyselected protection groups. It is appreciated by one skilled in the artthat by suitable protection, a functional entity may carry a wide rangeof substitutents.

The Functional Entity Precursor is a masked Functional Entity that isincorporated into an encoded molecule. After incorporation, reactiveelements of the Functional Entity may be revealed by un-masking allowingfurther synthetic operations. Finally, elements mediating recognition ofhost molecules may be un-masked.

The function of the carrier is to ensure the transferability of thefunctional entity. To adjust the transferability a skilled chemist candesign suitable substitutions of the carrier by evaluation of initialattempts. The transferability may be adjusted in response to thechemical composition of the functional entity, to the nature of thecomplementing element, to the conditions under which the transfer andrecognition is performed, etc.

In a preferred embodiment, the carrier is selected from the groupconsisting of:

wherein

-   W is —O—, —S—, —CR¹R¹—, —C(═O)—, —C(═S)—, —C(═NR²)— or —NR¹—;-   V is —N═, —CR¹═;-   P, Q and T are independently absent or are independently chosen from    —CR¹R¹—, —NR¹—, —O—, —S— or —PR¹—;-   M is B, Si or Sn;-   L is C₁-C₆ alkyl, -Aryl or —F-   n is 1 or 2; o is an integer between 2 and 10;

Due to practical reasons, a more preferred embodiment of the inventioncomprise compounds where the carrier is selected from the groupconsisting of:

wherein

-   W is —CR¹R¹′—, —C(═O)—, —C(═S)—, —C(═NR²)— or —NR¹—;-   P and Q are independently chosen from —CR¹R¹′—, —NR¹—, —O—, —S— or    —PR¹—;-   M is B, Si or Sn;-   L is C₁-C₆ alkyl, -Aryl or —F;-   n is 1 or 2;

4. A compound according to claim 1 wherein the Spacer is a valence bond,C₁-C₆ alkylene-A-, C₂-C₆ alkenylene-A-, C₂-C₆ alkynylene-A-, or

said spacer optionally being connected through A to a linker selectedfrom

where A is a valence bodn, —C(O)N—, —N—, —O—, —S—, or —C(O)—O—; B is avalence bond, —O—, —S—, —N— or —C(O)N— and connects to S—C-connectinggroup; R⁸ is selected independently from H, C₁-C₆ alkyl, C₃-C₇cycloalkyl, aryl or C₁-C₆ alkylene-aryl and n and m independently areintegers ranging from 1 to 10,

5. A compound according to claim 1 wherein the S—C-connecting group is avalence bond, —NH—C(═O)—, —NH—C(═O)—C₁-C₆ alkylene-, —S—S—, —S—S—C₁-C₆alkylene-, —C(═O)—NH—, —C(═O)—NH—(C₁-C₆ alkylene)-,

—NH—C(═O)-Arylene-C( )₂—NH—C(═O)—.

In another more preferred embodiment of the invention, the carrier is-Aryl-B(L)₂-where L is independently chosen from aryl or —F.

The S—C-connecting group provide a means for connecting the Spacer andthe Carrier. As such it is primarily of synthetic convenience and doesnot influence the function of a building block.

The spacer serves to distance the functional entity to be transferredfrom the bulky complementing element. Thus, when present, the identityof the spacer is not crucial for the function of the building block. Itmay be desired to have a spacer which can be cleaved by light. In thisoccasion, the spacer is provided with e.g. the group

In the event an increased hydrophilicity is desired the spacer may beprovided with a polyethylene glycol part of the general formula:

In a preferred embodiment, the complementing element serves the functionof recognising a coding element. The recognition implies that the twoparts are capable of interacting in order to assemble a complementingelement—coding element complex. In the biotechnological field a varietyof interacting molecular parts are known which can be used according tothe invention. Examples include, but are not restricted toprotein-protein interactions, protein-polysaccharide interactions,RNA-protein interactions, DNA-DNA interactions, DNA-RNA interactions,RNA-RNA interactions, biotin-streptavidin interactions, enzyme-ligandinteractions, antibody-ligand interaction, protein-ligand interaction,ect.

The interaction between the complementing element and coding element mayresult in a strong or a weak bonding. If a covalent bond is formedbetween the parties of the affinity pair the binding between the partscan be regarded as strong, whereas the establishment of hydrogenbondings, interactions between hydrophobic domains, and metal chelationin general results in weaker bonding. In general relatively weak bondingis preferred. In a preferred aspect of the invention, the complementingelement is capable of reversible interacting with the coding element soas to provide for an attachment or detachment of the parts in accordancewith the changing conditions of the media.

In a preferred aspect of the invention, the interaction is based onnucleotides, i.e. the complementing element is a nucleic acid.Preferably, the complementing element is a sequence of nucleotides andthe coding element is a sequence of nucleotides capable of hybridisingto the complementing element. The sequence of nucleotides carries aseries of nucleobases on a backbone. The nucleobases may be any chemicalentity able to be specifically recognized by a complementing entity. Thenucleobases are usually selected from the natural nucleobases (adenine,guanine, uracil, thymine, and cytosine) but also the other nucleobasesobeying the Watson-Crick hydrogen-bonding rules may be used, such as thesynthetic nucleobases disclosed in U.S. Pat. No. 6,037,120. Examples ofnatural and non-natural nucleobases able to perform a specific pairingare shown in FIG. 2. The backbone of the sequence of nucleotides may beany backbone able to aggregate the nucleobases is a sequence. Examplesof backbones are shown in FIG. 4. In some aspects of the invention theaddition of non-specific nucleobases to the complementing element isadvantegeous, FIG. 3.

The coding element can be an oligonucleotide having nucleobases whichcomplements and is specifically recognised by the complementing element,i.e. in the event the complementing element contains cytosine, thecoding element part contains guanine and visa versa, and in the eventthe complementing element contains thymine or uracil the coding elementcontains adenine.

The complementing element may be a single nucleobase. In the generationof a library, this will allow for the incorporation of four differentfunctional entities into the template-directed molecule. However, toobtain a higher diversity a complementing element preferably comprisesat least two and more preferred at least three nucleotides.Theoretically, this will provide for 4² and 4³, respectively, differentfunctional entities uniquely identified by the complementing element.The complementing element will usually not comprise more than 100nucleotides. It is preferred to have complementing elements with asequence of 3 to 30 nucleotides.

The building blocks of the present invention can be used in a method fortransferring a functional entity to a recipient reactive group, saidmethod comprising the steps of

-   -   providing one or more building blocks as described above and    -   contacting the one or more building blocks with a corresponding        encoding element associated with a recipient reactive group        under conditions which allow for a recognition between the one        or more complementing elements and the encoding elements, said        contacting being performed prior to, simultaneously with, or        subsequent to a transfer of the functional entity to the        recipient reactive group.

The encoding element may comprise one, two, three or more codons, i.e.sequences that may be specifically recognised by a complementingelement. Each of the codons may be separated by a suitable spacer group.Preferably, all or at least a majority of the codons of the template arearranged in sequence and each of the codons are separated from aneighbouring codon by a spacer group. Generally, it is preferred to havemore than two codons on the template to allow for the synthesis of morecomplex encoded molecules. In a preferred aspect of the invention thenumber of codons of the encoding element is 2 to 100. Still morepreferred are encoding elements comprising 3 to 10 codons. In anotheraspect, a codon comprises 1 to 50 nucleotides and the complementingelement comprises a sequence of nucleotides complementary to one or moreof the encoding sequences.

The recipient reactive group may be associated with the encoding elementin any appropriate way. Thus, the reactive group may be associatedcovalently or noncovalently to the encoding element. In one embodimentthe recipient reactive group is linked covalently to the encodingelement through a suitable linker which may be separately cleavable torelease the reaction product. In another embodiment, the reactive groupis coupled to a complementing element, which is capable of recognising asequence of nucleotides on the encoding element, whereby the recipientreactive group becomes attached to the encoding element byhybridisation. Also, the recipient reactive group may be part of achemical scaffold, i.e. a chemical entity having one or more reactivegroups available for receiving a functional entity from a buildingblock.

The recipient reactive group may be any group able to participate incleaving the bond between the carrier and the functional entityprecursor to release the functional entity precursor. Usually, thereactive group is an electronegative atom such as —OR, —F, —Cl, —Br or—I where R is a substituted sulfonyl group (ie.—OR comprises -OMs, -OTfand -OTos) activated by a transition metal such as Pd, Pt, Ni, Cu, Rh orRu. Typically, the reactive group is attached to an aromatic- orheteroaromatic ring (Scheme 1) or a C—C double bond (Scheme 2). Scheme 3shows an alkyl or alkenyl Functional Entity replacing a reactiverecipient group attached to an aryl.

Also aldehydes or imines may serve as recipient reactive groupoptionally in the presence of a catalyst.

According to a preferred aspect of the invention the building blocks areused for the formation of a library of compounds. The complementingelement of the building block is used to identify the functional entity.Due to the enhanced proximity between reactive groups when thecomplementing entity and the encoding element are contacted, thefunctional entity together with the identity programmed in thecomplementing element is transferred to the encoding element associatedwith recipient reactive group. Thus, it is preferred that the sequenceof the complementing element is unique in the sense that the samesequence is not used for another functional entity. The uniqueidentification of the functional entity enable the possibility ofdecoding the encoding element in order to determine the synthetichistory of the molecule formed. In the event two or more functionalentities have been transferred to a scaffold, not only the identity ofthe transferred functional entities can be determined. Also the sequenceof reaction and the type of reaction involved can be determined bydecoding the encoding element. Thus, according to a preferred embodimentof the invention, each different member of a library comprises acomplementing element having a unique sequence of nucleotides, whichidentifies the functional entity.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1. Two setups for Functional Entity Transfer

FIG. 2. Examples of specific base pairing

FIG. 3. Example of non-specific base-pairing

FIG. 4. Backbone examples

DETAILED DESCRIPTION OF THE INVENTION

A building block of the present invention is characterized by itsability to transfer its functional entity to a recipient reactive group.This is done by forming a new covalent bond between the recipientreactive group and cleaving the bond between the carrier moiety and thefunctional entity of the building block.

Two setups for generalized functional entity transfer from a buildingblock are depicted in FIG. 1. In the first example, one complementingelement of a building block recognizes a coding element carrying anotherfunctional entity, hence bringing the functional entities in closeproximity. This results in a reaction between functional entity 1 and 2forming a covalent bond between these concurrent with the cleavage ofthe bond between functional entity 2 and its linker. In the secondexample, a coding element brings together two building blocks resultingin functional entity transfer from one building block to the other.

EXPERIMENTAL SECTION

Assembly of Building Blocks

The Carrier-Functional Entity ensemble may be bound to the Spacer byseveral different reactions as illustrated below.Formation of an Amide Bond between a Carboxylic Acid of the Carrier andan Amine Group of a Spacer

General Procedure 1: Preparation of Neutral Boronic Ester Derivatives(I):

4-[(3-Hydroxy-2-hydroxymethyl-2-methyl-propionylamino)-methyl]-benzoicacid benzyl ester (0.59 mmol, 210 mg) and aryl boronic acid (0.60 mmol)is mixed in toluene (15 mL) and stirred 16 h at 70° C. The product isobtained by evaporation of the solvent under reduced pressure.

The aryl boronic acid derivate (0.12 mmol) is dissolved in methanol andtransferred to an autoclave. A catalytic amount of palladium onactivated carbon (5 wt. %) is added to the solution under an argonatmosphere. The argon is exchanged with hydrogen and the reaction isperformed at room temperature for 24 hours under a pressure of 50 barsaffording I upon filtration and removal of the solvent.

Example 1 General Procedure (1)4-({[2-(4-Fluoro-phenyl)-5-methyl-[1,3,2]dioxaborinane-5-carbonyl]-amino}-methyl)benzoicacid

Yield 90% (0.11 mmol, 40 mg). ¹H-NMR (DMSO-d₆): 8.59 (t, 1H); 7.70-7.11(m, 8H); 4.44 (d, 2H); 4.36 (d, 2H); 3.96 (d, 2H); 1.13 (s, 3H)Synthesis of the Boronic Ester Ligand (II):

Isopropylidene-2,2-bis(hydroxymethyl)propionic acid:

2,2-Bis(hydroxymethyl)propionic acid (0.12 mol, 15.9 g) was refluxed inacetone (250 mL) with molecular sieves and conc. sulphuric acid (0.5 mL)for 10 hours. The reaction mixture was then neutralised with NaHCO₃ (1 Maq.), stirred with activated charcoal and filtered. The product wascollected as a white crystalline upon concetration of the solvent.

Yield 50% (10.5 g): ¹H-NMR (DMSO-d₆): 1.07 (s, 3H, —CH₃); 1.26 (s, 3H,—CH₃); 1.34 (s, 3H, —CH₃); 3.53 and 3.57 (d, 2H, —CH₂—); 3.99 and 4.02(d, 2H, —CH₂—).

4-(Boc-amino-methyl)-benzoic acid:

4-Methylaminobenzoic acid was dissolved in dioxane (10 mL) and NaOH (22mL, 1M solution) and cooled to 0° C. Ditertbutyl dicarbonate (10 mmol,2.18 g) and NaOH (8 mL, 2M solution) was added, and the reaction mixturewas left over night at room temperature. Half of the solvent was removedunder reduced pressure and ethylacetate added (25 mL). The reactionmixture was then neutralised by adding HCl (2 M solution) to pH=4, andextracted with ethyl acetate (3×75 mL). The organic phase was dried, andevaporated to dryness, and the product was obtained as a whitecrystalline solid.

Yield: 65% (6.0 mmol, 1.51 g): ¹H-NMR (DMSO-d₆): 12.84 (s, 1H); 7.89 (d,2H); 7.46 (t, 1H); 7.34 (d, 2H); 4.19 (d, 2H); 1.40 (s, 9H).

4-[(Boc-amino)-methyl]-benzoic acid benzyl ester:

4-[(Boc-amino)-methyl]-benzoic acid (5.89 mmol, 1.48 g) in anhydrous DMF(20 mL) was added Cs₂CO₃ (2.95 mmol, 0.96 g) and stirred for 1 h at roomtemperature. Benzyl bromide (8.2 mmol, 1.0 mL) was added, and thereaction stirred for 9 hours. The solvent was removed under reducedpressure, and the crude was suspended in water (100 mL) and extractedwith diethyl ether (3×100 mL). The organic phase was then dried,evaporated to dryness and the obtained product was purified using drycolumn vacuum chromatography.

Yield=81% (4.79 mmol, 1.56 g): ¹H-NMR (DMSO-d₆): 7.95 (d, 2H); 7.48-7.37(m, 7H); 5.35 (s, 2H); 4.20 (d, 2H); 1.39 (s, 9H).

4-Methylamino benzoic acid benzyl ester:

N-Boc-4-methylamino benzoic benzyl ester (4.79 mmol, 1.55 g) wasdissolved in DCM (25 mL) with TFA (10% v/v) and triethylsilane (1% v/v)and stirred for 30 minutes. The solvent was removed under reducedpressure and the product purified using dry column vacuumchromatography.

Yield=47% (2.28 mmol, 550 mg): ¹H-NMR (DMSO-d₆): 8.69 (s, 2H); 8.03 (d,2H); 7.62 (d, 2H); 7.50-7.36 (m, 5H); 5.37 (s, 2H); 4.14 (s, 2H).

4-{[(2,2,5-Trimethyl-[1,3]dioxane-5-carbonyl)-amino]-methyl}benzoic acidbenzyl ester

Isopropylidene-2,2-bis(hydroxymethyl)propionic acid (4.10 mmol, 714 mg)and 4-methylamino benzyloxy benzoic acid (4.14 mmol, 1.0 g) in DCM (20mL) was cooled to 0° C. and diisopropyl carbodiimide (5.5 mmol, 0.7 mL)was added. The reaction mixture was left over night at room temperature,and the solvent was removed under reduced pressure. The crude wasdissolved in toluene and filtered. The filtrate was purified using DryColumn Vacuum Chromatography.

Yield=29% (478 mg): ¹H-NMR (DMSO-d₆): 8.25 (t, 1H); 7.93 (d, 2H);7.47-7.35 (m, 9H); 5.34 (s, 2H); 4.39 (d, 2H); 4.04 (d, 2H); 3.65 (d,2H); 1.37 (s, 3H); 1.29 (s, 3H); 1.05 (s, 3H);

4-[(3-Hydroxy-2-hydroxymethyl-2-methyl-propionylamino)-methyl]-benzoicacid benzyl ester

4-{[(2,2,5-Trimethyl-[1,3]dioxane-5-carbonyl)-amino]-methyl}-benzoicacid benzyl ester (1.2 mmol, 478 mg) was dissolved in acetic acid (11.5mL, 87% v/v) and stirred at 40° C. for 3 hours. The product II wasobtained by evaporation of the reaction mixture under reduced pressureand co evaporation from anhydrous toluene (3×20 mL).

Yield=90%: ¹H-NMR (DMSO-d₆): 8.07 (t, 1H); 7.92 (d, 2H); 7.48-7.12 (m,7H); 5.34 (s, 2H); 4.72 (bs, 2H); 4.37 (d, 2H); 3.46 (m, 4H); 1.04 (s,3H).

Example 2 General procedure (1)

Synthesis of the Boronic Ester Ligand (III):

3-[Bis-(3-hydroxy-propyl)-amino]-propionic acid benzyl III ester issynthesised according to literature procedures from the corresponding3-amino-propionic acid benzyl ester (Goldschmidt; Veer; RTCPA3; Recl.Trav. Chim. Pays-Bas; 1948, 67, 489.)General Procedure 2: Synthesis of Flouroborate Cesium Salt Derivatives:

Caesium fluoride (18 mg, 0.12 mmol) is added to a stirred solution ofthe aryl boronic ester derivate (0.12 mmol) in DMF (4 mL) at 85° C. Themixture is stirred for 3 hours. The product precipitates from solutionduring evaporation of the solvent under reduced pressure. Uponfiltration the product was filtered and washed with diethyl ether.

Example 3 General procedure (2)

Yield=40% (0.048 mmol, 25 mg) ¹H-NMR (DMSO-d₆): 8.06 (t, 1H); 7.88-7.14(m, 8H); 4.73 (t, 2H); 4.45 (d, 1H); 4.36 (d, 2H); 3.97 (d, 1H); 1.04(s, 3H).

¹⁹F-NMR (DMSO-d₆): −74.75, −109.76, −118.89, −139.00, −148.28.General Procedure 3: Synthesis of Fluoroborate Potassium SaltDerivatives:

Potassium hydride (80 mg, 2.0 mmol) is added to a stirred solution of4-[(3-hydroxy-2-hydroxymethyl-2-methyl-propionylamino)-methyl]-benzoicacid benzyl ester II (357 mg, 1.0 mmol) in anhydrous acetonitrile (10mL) at room temperature. Potassium aryltrifluoroborate (1.0 mmol) wasadded to the reaction mixture, followed by chlorotrimethylsilane (231μL, 2.0 mmol). The mixture is stirred for 2 hour at room temperature andthen diluted with ethyl acetate (40 mL), washed with distilled water(2×40 mL) and dried over sodium sulphate (anhydrous). Removal of solventyields a crude product which is purified by dissolving in hot acetoneand precipitating with petroleum ether.

The fluoroborate potassium salt derivate (0.5 mmol) is dissolved inmethanol and transferred to an autoclave. A catalytic amount ofpalladium on activated carbon (5 wt. %) is added to the solution underan argon atmosphere. The argon was exchanged with hydrogen and thereaction is performed at room temperature for 24 hours under a pressureof 50 bars affording the desired product upon filtration and removal ofthe solvent.General Procedure 4: Synthesis of Fluoroborate Potassium SaltDerivatives:

Chlorotrimethyl silane (231 μL, 2.0 mmol) is added to a stirred solutionof potassium aryltrifluoroborate (IV) (1.0 mmol) and4-acetyl-5-oxo-hexanoic acid benzyl ester (262 mg, 1.0 mmol) inanhydrous acetonitrile (10 mL) at room temperature under an atmosphereof nitrogen. The mixture is stirred for 1 hour at room temperature andthen diluted with ethyl acetate (40 mL), washed with distilled water(2×40 mL) and dried over sodium sulphate. Removal of solvent gives acrude product, which was subjected to plug filtration on silica gel(dichloromethane/heptane 50:50). The fluoroborate derivate (0.5 mmol) isdissolved in methanol and transferred to an autoclave. A catalyticamount of palladium on activated carbon (5 wt. %) is added to thesolution under an argon atmosphere. The argon is exchanged with hydrogenand the reaction is performed at room temperature for 24 hours under apressure of 50 bars affording the desired product upon filtration andremoval of the solvent.

Example 4

To a stirred solution of potassium phenyltrifluoroborate (204 mg, 1.11mmol) and methyl 4-acetyl-5-oxo-hexanoate (194 μL, 1.11 mmol) inanhydrous acetonitrile (5 mL) was added chlorotrimethyl silane (257 μL,2.22 mmol) at room temperature under an atmosphere of nitrogen. Themixture was stirred overnight at room temperature and then diluted withethyl acetate (20 mL), washed with distilled water (2×20 mL) and driedover sodium sulphate. Removal of solvent gave an oil, which wassubjected to plug filtration on silica gel (dichloromethane/heptane50:50) to give.

Yield=37%: ¹H-NMR (CDCl₃): 7.55 (dd, 2H); 7.38-7.30 (m, 3H); 3.72 (s,3H); 2.76-2.71 (m, 2H); 2.52-2.47 (m, 2H); 2.40 (s, 6H); ¹⁹F-NMR(CDCl₃): −143.7 (s) (without internal standard).General Procedure 5: Preparation of Difluoroborate Potassium SaltDerivatives (V):

To a stirred solution of potassium aryltrifluoroborate (VI) (1.0 mmol)in anhydrous THF is added TMSCl (1.0 mmol) at room temperature under anatmosphere of nitrogen. After 1 h, the mixture is cooled to −10° C. andaryl magnesiumbromide (1.0 mmol) is added. The mixture is stirred for 1hour at room temperature and then diluted with ethyl acetate (40 mL),washed with distilled water (2×40 mL) and dried over sodium sulphate(anhydrous). Removal of solvent gives a crude product which is purifiedby dissolving in hot acetone and precipitating with petroleum ether. Thedifluoroborate potassium salt derivate (0.5 mmol) is dissolved inmethanol and transferred to an autoclave. A catalytic amount ofpalladium on activated carbon (5 wt. %) is added to the solution underan argon atmosphere. The argon is exchanged with hydrogen and thereaction is performed at room temperature for 24 hours under a pressureof 50 bars affording the desired product upon filtration and removal ofthe solvent.Synthesis of Borate (VI):

The potassium aryltrifluoroborate (VI) was synthesised in according toliterature procedures from the corresponding 2-iodo-benzoic acid.(Molander, G. A.; Biolatto, B. Org. Lett. 2002, 4, 1867., Molander, G.A.; Katona, B. W.; Machrouhi, F. J. Org. Chem. 2002, 67, 8416.,Molander, G. A.; Bernardi, C. J. Org. Chem. 2002, 67, 8224.)

Yield=35%: ¹H-NMR (DMSO-d₆): 7.48-7.44 (m, 3H); 7.35-7.27 (m, 3H); 7.20(d, 2H); 7.12-7.09 (m, 1H); 5.16 (s, 1H); ¹⁹F-NMR (DMSO-d₆): −137.20 (m)(without internal standard).

Example 5

The oxazaborolidinone VII is synthesised according to literatureprocedures for the corresponding sodium salt of4-[(N-carboxymethyl-formimidoyl)-methyl-amino]-benzoic acid benzyl esterVII and potassium aryltrifluoroborate.(Vedejs, E.; Chapman, R. W.;Fields, S. C.; Lin, S.; Schrimpf, M. R. J. Org. Chem. 1995, 60, p 3020.)Synthesis of Ligands for Oxazaborolidinones:

The 4-(dimethoxymethyl methyl-amino)-benzoic acid benzyl ester issynthesised according to literature procedures from the corresponding4-methylamino-benzoic acid.(Scheeren, J. W.; Nivard, R. J. F.; RTCPA3;Recl. Trav. Chim. Pays-Bas; 1969, 88, 3, 289.) The acetal derivate fromthe first step (315 mg, 1.0 mmol) is dissolved in dichloromethane (10mL) followed by addition of benzyl alcohol (119 mg, 1.1 mmol), DCC (227mg, 1.1 mmol) and DMAP (12.2 mg, 0.1 mmol). The reaction mixture isstirred overnight at 25° C. The solvent is evaporated under reducedpressure and the crude purified on column chromatography using silicagel.

The sodium salt of4-[(N-carboxymethyl-formimidoyl)-methyl-amino]-benzoic acid benzyl esteris synthesised in according to literature procedures from thecorresponding 4-(dimethoxymethyl-methyl-amino)-benzoic acid benzyl esterand the sodium salt of glycine. (Vedejs, E.; Chapman, R. W.; Fields, S.C.; Lin, S.; Schrimpf, M. R. J. Org. Chem. 1995, 60, p 3020.)General Procedure 6: Preparation of Building Blocks by Loading aCarrier-Functional Entity Ensemble onto a Nucleotide DerivativeComprising an Amino Group:

15 μL of a 150 mM building block solution of FE¹-Carrier-COOH is mixedwith 15 μL of a 150 mM solution of EDC and 15 μL of a 150 mM solution ofN-hydroxysuccinimide (NHS) using solvents like DMF, DMSO, water,acetonitril, THF, DCM, methanol, ethanol or a mixture thereof. Themixture is left for 15 min at 25° C. 45 μL of an aminooligo (10 nmol) in100 mM buffer at a pH between 5 and 10, preferably 6.0-7.5 is added andthe reaction mixture is left for 2 hours at 25° C. Excess building blockand organic by-products were removed by extraction with EtOAc (400 μL).Remaining EtOAc is evaporated in vacuo using a speedvac. The buildingblock is purified following elution through a BioRad micro-spinchromatography column, and analyzed by electron spray mass spectrometry(ES-MS).

Use of Building Blocks

General Procedure 7: C—C Coupling Between Oligonucleotide DerivativesContaining an Recipient Reactive Group and a Building Block According tothe Invention:

An oligonucleotide building block carrying functional entity FE¹ iscombined at 2 μM final concentration with one equivalent of acomplementary building block displaying an organo-halide ororgano-triflate. Reaction proceeds at temperatures between 0° C. and100° C. preferably between 15° C.-50° C. for 148 hours, preferably 10-20hours in DMF, DMSO, water, acetonitril, THF, DCM, methanol, ethanol or amixture thereof, pH buffered to 4-10, preferably 6-8 in the presence ofa Pd catalyst. Organic by-products are removed by extraction with EtOAc,followed by evaporation of residual organic solvent for 10 min in vacuo.Pd catalyst is removed and oligonucleotides are isolated by elutingsample through a BioRad micro-spin chromatography column. Couplingefficiency is quantified by ES-MS analysis.

Example 6 An Illustration of the Entire Process from Building BlockSynthesis to Functional Entity Transfer

Nucleophilic monomer building blocks capable of transferring an aryl,hetaryl or vinyl functionality may be prepared from organic buildingblocks type (3). This is available by estrification of a boronic acid bya diol e.g. (1), followed by transformation into the NHS-esterderivative. The NHS-ester derivative may then be coupled to anoligonucleotide to generate monomer building block type (5).Alternatively, the carboxylic acid (2) may be used in general procedure6.

Likewise, building block 4 may be prepared via an NHS-ester or bygeneral procedure 6:

The transtion metal catalyzed cross coupling is conducted as follows:

A premix of 1.4 mM Na₂PdCl₄ and 2.8 mM P(p-SO₃C₆H₄)₃ in water left for15 min was added to a mixture of the template oligonucleotide (1 nmol)and monomer building block (4) and (5) (both 1 nmol) in 0.5 M NaOAcbuffer at pH=5 and 75 mM NaCl (final [Pd]=0.3 mM). The mixture is thenleft o/n at 35-65° C. preferably 58° C., to yield template bound (6).

R=aryl, hetaryl or vinyl Abbreviations DCC N,N′-DicyclohexylcarbodiimideDhbtOH 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-benzotriazine DICDiisopropylcarbodiimide DIEA Diethylisopropylamin DMAP4-Dimethylaminopyridine DNA Deoxyribosenucleic Acid EDC1-Ethyl-3-(3′-dimethylaminopropyl)carbodiimide.HCl HATU2-(1H-7-Azabenzotriazole-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate HBTU2-(1H-Benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphateHOAt N-Hydroxy-7-azabenzotriazole HOBt N-Hydroxybenzotriazole LNA LockedNucleic Acid NHS N-hydroxysuccinimid OTf Trifluoromethylsulfonate OTsToluenesulfonate PNA Peptide Nucleic Acid PyBoPBenzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphatePyBroP Bromo-tris-pyrrolidino-phosphonium hexafluorophosphate RNARibonucleic acid TBTU2-(1H-Benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborateTEA Triethylamine RP-HPLC Reverse Phase High Performance LiquidChromatography TBDMS-CI Tert-Butyldimethylsilylchloride 5-Iodo-dU5-iodo-deoxyriboseuracil TLC Thin layer chromatography (Boc)₂O Bocanhydride, di-tert-butyl dicarbonate TBAF Tetrabutylammonium fluorideSPDP Succinimidyl-propyl-2-dithiopyridyl

1. A building block of the general formulaComplementing Element-Linker-Carrier-Functional entity precursor capableof transferring a functional entity to a recipient reactive group,wherein Complementing Element is a group identifying the functionalentity, Linker is a chemical moiety comprising a spacer and aS—C-connecting group, wherein the spacer is a valence bond or a groupdistancing the functional entity precursor to be transferred from thecomplementing element and the S—C-connecting group connects the spacerwith the Carrier, Carrier comprises an aromatic-, a saturated- or apartially saturated heterocyclic ring system, said ring system beingmono-, di- or tricyclic and substituted with 0-3 R¹ and containing aring-member M belonging to the group consisting of B, Si, Sn and Zn,whereas M carries the functional entity precursor and 0-2 ligands Lselected independently from the group consisting of —F, -aryl,-heteroaryl, or Carrier is —Ar-M(L)_(p)—, —Ar-(C₁-C₆ alkylene)-M(L)_(p)—or —Ar—X—(C₁-C₆ alkylene)-M(L)_(p)— where Ar is aryl or heteroarylsubstituted with 0-3 R¹, M² is B, Sn or Si, X is O, S, or R² and L isindependently chosen from —F, -aryl, -heteroaryl or C₁-C₆ alkyl; R¹ andR^(1′) are independently selected from —H, —O R², —N R² ₂, -Halogen,—NO₂, —CN, —C(Halogen)₃, —C(O)R², —C(O)NHR², C(O)NR² ₂, —NC(O)R²,—S(O)₂NHR², —S(O)₂NR² ₂, —S(O)₂R², —P(O)₂—R², —P(O)—R², —S(O)—R²,P(O)—OR², —S(O)—OR², N⁺R² ₃, wherein p is an integer of 0 to 3 and R² isH, C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, or aryl, Functional entityprecursor is H or selected among the group consisting of a C₁-C₆ alkyl,C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₄-C₈ alkadienyl, C₃-C₇ cycloalkyl, C₃-C₇cycloheteroalkyl, aryl, and heteroaryl, said group being substitutedwith 0-3 R³, 0-3 R⁴ and 0-3 R⁷ or C₁-C₃ alkylene-NR³ ₂, C₁-C₃alkylene-NR³C(O)R⁶, C₁-C₃ alkylene-NR³C(O)OR⁶, C₁-C₂ alkylene-O—N R³ ₂,C₁-C₂ alkylene-O—NR³C(O)R⁶, C₁-C₂ alkylene-O—N R³C(O)OR⁶ substitutedwith 0-3 R⁷. where R³ is H or selected independently among the groupconsisting of C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₇cycloalkyl, C₃-C₇ cycloheteroalkyl, aryl, heteroaryl, said group beingsubstituted with 0-3 R⁴ and 0-3 R⁷ R⁴ is selected independently from—N₃, —CNO, —C(NOH)NH₂, —NHOH, —NHNH, —C(O), —P(O)(O)₂ or the groupconsisting of C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₄-C₈ alkadienyl said groupbeing substituted with 0-2 R⁵, R⁵ is independently selected from —NO₂,—C(O)O, —C(O), —CN, —OSi₃, —O and —N₂, and R⁶ is H, C₁-C₆ alkyl, C₂-C₆alkenyl, C₂-C₆ alkynyl, C₃-C₇ cycloalkyl, aryl or C₁-C₆ alkylene-arylsubstituted with 0-3 substituents independently selected from —F, —Cl,—NO₂, —R², —OR², —SiR² ₃, and R⁷ is ═O, —F, —Cl, —Br, —I, —CN, —NO₂, -O,—N₂, —N—C(O)R⁶, —N—C(O)OR⁶, —S, —(O), —S(O)₂, —COO, —C(O)N₂, or—S(O)₂N₂.
 2. A compound according to claim 1 wherein, the carrier isselected from the group consisting of:

wherein W is —O—, —S—, —CR¹R¹′—, —C(═O)—, —C(═S)—, —C(═NR² or —NR¹—; Vis —N═, —CR¹═; P, Q and T are independently absent or are independentlychosen from —CR¹R¹′—, —NR¹—, —O—, —S— or —PR¹—; M is B, Si or Sn; L isC₁-C₆ alkyl, -Aryl or —F; n is 1 or 2; o is an integer between 2 and 10.3. A compound according to claim 1 wherein, the carrier is selected fromthe group consisting of:

wherein W is —CR¹R¹′—, —C(═O)—, —C(═S)—, —C(═NR²)— or —NR¹—; P and Q areindependently chosen from —CR¹R¹′—, —NR¹—, —O—, —S—or —PR¹—; M is B, Sior Sn; L is C₁-C₆ alkyl, -Aryl or —F; n is 1 or
 2. 4. A compoundaccording to claim 1 wherein the Spacer is a valence bond, C₁-C₆alkylene-A-, C₂-C₆ alkenylene-A-, C₂-C₆ alkynylene-A-, or

said spacer optionally being connected through A to a linker selectedfrom

where A is a valence bodn, —C(O)N—, —N—, —O—, —S—, or —C(O)—O—; B is avalence bond, —O—, —S—, —N— or —C(O)N— and connects to S—C-connectinggroup; R⁸ is selected independently from H, C₁-C₆ alkyl, C₃-C₇cycloalkyl, aryl or C₁-C₆ alkylene-aryl and n and m independently areintegers ranging from 1 to
 10. 5. A compound according to claim 1wherein the S—C-connecting group is a valence bond, —NH—C (═O)—, —NH—C(═O)—C₁-C₆ alkylene-, —S—S—, —S—S—C₁-C₆ alkylene-, —C (═O)—NH—, —C(═O)—NH— (C₁-C₆ alkylene)-,

—NH—C(═O)-Arylene-C( )₂—NH—C(═O)—.
 6. A compound according to claim 1wherein, the carrier is -Aryl-B(L)₂— where L is independently chosenfrom aryl or —F.
 7. A compound according to claim 1 where Complementingelement is a nucleic acid.
 8. A compound according to claim 1 whereComplementing element is a sequence of nucleotides selected from thegroup consisting of DNA, RNA, LNA, PNA, and morpholino derivatives.
 9. Alibrary of compounds according to claim 1, wherein each different memberof the library comprises a complementing element having a uniquesequence of nucleotides, which identifies the functional entity.
 10. Amethod for transferring a functional entity to a recipient reactivegroup, comprising the steps of providing one or more building blocksaccording to claim 1, contacting the one or more building blocks with acorresponding encoding element associated with a recipient reactivegroup under conditions which allow for a recognition between the one ormore complementing elements and the encoding elements, said contactingbeing performed prior to, simultaneously with, or subsequent to atransfer of the functional entity to the recipient reactive group. 11.The method according to claim 10, wherein the encoding element comprisesone or more encoding sequences comprised of 1 to 50 nucleotides and theone or more complementing elements comprises a sequence of nucleotidescomplementary to one or more of the encoding sequences.
 12. The methodof claim 10, wherein the recipient reactive group is an aromatic halogensubstituent selected from the group consisting of Br and I, which may bepart of a chemical scaffold, and the activating catalyst containspalladium.